Search

The Covid-19 pandemic instills emotions that can be understood in the pathological sense of mental disorder and/or in the heuristic sense of a moral dimension. So what about this distinction in critical care and resuscitation services where caregivers are at the forefront of events? What to do with emotions? The objective of this work is to pose a medico-psychological and ethical perspective on these questions, starting from the hypothesis that emotions have a specific use during the pandemic. The first step will be to show that anguish and fear, although different from an epistemological point of view, arise from the same historical place, which is the discourse of the medical world with death. The awareness of the inevitable makes share the same need of the caregiver and the citizen of a psychic economy which will lead to differentiating two possible reactions to emotions: one to face up and one to come to terms with. This psychic interlacing, inherent to the pandemic context, calls for critical care on a moral dimension related to the issue of abandonment of the human person and the poorly understood notion of "mass death". An answer to this difficulty would be found in the concept of "being-caregiver-close" but its application also supposes an ethical reflection on the outlets and the personal virtues., (© 2021 Elsevier Masson SAS. All rights reserved.)

Introduction: Anti-tumoral immunotherapy is currently the basis of a profound modification of therapeutic concepts in oncology, in particular since the arrival of immune checkpoint inhibitors (ICI). In addition to their efficacy profile, these immune-targeted agents also generate adverse events. With the increasing use of ICI for a growing number of tumor types, awareness of immunotherapy-related adverse events is essential to ensure prompt diagnosis and effective management of these potentially serious adverse events., Background: Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) are two co-inhibitory receptors that are expressed on activated T cells against which therapeutic blocking antibodies have reached routine clinical use. Immune checkpoint blockade can induce inflammatory adverse effects, termed immune-related adverse events (irAEs), which resemble autoimmune disease. Though severe irAEs remain rare, they can be fatal if not diagnosed and treated in an appropriate manner., Outlook and Conclusion: Additional studies are needed to better understand the clinical characteristics and chronology of these adverse effects and to clarify their pathophysiological mechanisms., (Copyright © 2018 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Occupational health and safety (OHS) information is often complex, diverse and unstructured and suffers from a lack of integration which usually precludes any systemic insight of the situation., Aims: To analyse to what extent the use of geographical information systems (GISs) can help to integrate, analyse and present OHS data in a comprehensive and communicable way relevant for surveillance purposes., Methods: We first developed a 'macro-approach' (from national to local level), mapping data related to economic activity (denominator of active workers displayed by activity sectors), as well as work-related ill-health (numerators of workers suffering from work-related ill-health). The latter data are composed of compensated occupational diseases on the one hand and work-related diseases investigated by specialized clinics on the other hand. Then, a 'micro-approach' was worked out, integrating at a plant level, using computer-aided drawing, occupational risks data and OHS surveillance data (e.g. use of medication and sickness absence data)., Results: At the macro-level, microelectronics companies and workers were mapped at different scales. For the first time, we were able to compare, up to the enterprise level, complementary data showing different pictures of work-related ill-health, allowing a better understanding of OH issues in this sector. At the micro-level, new information arose from the integration of risk assessment data and medical data., Conclusions: This work illustrates to what extent GIS is a promising tool in the OHS field, and discusses related challenges (technical, ethical, biases and interpretation) and research perspectives., (© The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Surgery of limited metastatic lesions from malignant melanoma can achieve long-term remission and better survival than chemotherapy. Existing criteria for selection of candidate patients for this surgery do not seem sufficient to avoid useless excisions., Objectives: To test use of neoadjuvant chemotherapy as a new criterion in this setting., Methods: All patients who underwent thoracic surgery for one or two lung metastases from melanoma during 1999-2007 were included in the study. Demographic and medical data were collected and analysed. Several possible prognostic factors were evaluated based on the overall survival curves., Results: Thirteen patients were included in this retrospective study. All but two patients had no evidence of disease after surgery. Ten patients received neoadjuvant chemotherapy. Six responded (absence of progression) and four had progressive disease. Response to chemotherapy and no evidence of disease after surgery were predictive of long-term survival., Conclusions: Neoadjuvant chemotherapy can be considered as a new criterion for better selection of candidate patients for lung metastasis surgical resection. This would also avoid useless surgical procedures in rapidly progressive disease and give information on the chemosensibility of the metastatic disease. This study needs further confirmation, particularly with chemotherapy regimens that have demonstrated better objective responses.

Introduction: Twenty percent of melanoma are located on the head and neck. The treatment of advanced melanoma is still a controversial question. The aim of this study was to analyze the results of lymph node treatment in melanoma, and to try to determine guidelines for management., Patients and Methods: Sixteen male and 9 female patients (mean age 57.1 years) presenting with head and neck melanoma with parotid or cervical node involvement were treated by curative surgery., Results: Most tumors were classified intermediate according to the Breslow thickness. The average of nodes involved was 2.3 with 44% of cases presenting with capsular rupture. The mean follow-up was 32 months. The mean delay of recurrence was 18.2 months. The 5-year probability of survival was 49.7% and the one none-recurrence was 15.8%. Patients without capsular rupture had a better prognosis (P=0.04)., Discussion: The management of advanced melanoma of the head and neck is still controversial, but: 1-worse prognosis of patients with advanced melanoma; 2-percentage of occult metastasis was about 20; 3-better prognosis for patients with palpable nodes who had neck dissection and postoperative radiation in cases of node involvement. Until the sentinel node technique becomes widely accepted and performed we recommend: prophylactic dissection (cervical or parotidectomy) in patients with intermediate thickness and without palpable nodes; when patients have resectable node involvement a postoperative radiotherapy.

Introduction: Bullous forms of cutaneous T-cell lymphomas are rare. A new group of cutaneous T-cell lymphomas has recently been identified as a distinct clinicopathological and immunophenotype entity. These cutaneous T-cell lymphomas express a CD8+ phenotype, rarely expressed in other cutaneous T-cell lymphomas., Case Report: We describe a cutaneous CD8+ squamous T-cell lymphoma with polymorphic clinical features, strongly epidermotropic lymphoid infiltrate and spongiosis, classical for this type of lymphoma., Discussion: Bullous lesions in cutaneous T-cell lymphoma should evoke the possibility of a cutaneous CD8+ T-cell lymphoma, once other bullous diseases have been excluded. Spongiosis, rare in other types of T-cell lymphoma, and strongly epidermotropic pleomorphic lymphoid infiltrate are classical histological features. The association of polymorphic lesions, bullas and atypical CD8+ epidermotropic phenotype should evoke this diagnosis even at the early stage. Treatment is difficult and classical chemotherapy often fails. Prognosis is poor with a mean overall survival of 32 months.

Thin (

Background: Mechlorethamine is frequently used in the treatment of cutaneous lymphoma, but its application is limited in 30-80% of cases because of cutaneous intolerance. Reducing the concentration to avoid this side-effect has been only modestly successful., Objectives: To investigate whether a shorter application period could reduce the frequency of intolerance., Methods: In an open prospective study in 39 patients with cutaneous T-cell lymphoma or parapsoriasis, mechlorethamine was applied according to the usual practices of the participating physicians (number of weekly applications, treatment confined to lesions or performed over the entire body) and then washed off after 1 h in all cases., Results: Cutaneous intolerance was observed in 19 of 39 patients (49%). Six of these patients showed allergic contact dermatitis to mechlorethamine after a mean period of 9.3 weeks, while the other 13 developed irritant contact dermatitis after a longer period. Cutaneous intolerance did not differ significantly according to the number of applications per week or the extent of body area treated. The therapeutic response rate was 69%, and no difference in therapeutic efficacy was noted between daily and intermittent applications., Conclusions: Comparison with published studies showed no significant difference in the number of cases of cutaneous intolerance after short-term application, although their occurrence was delayed. Therapeutic response was decreased appreciably by short-term application as compared with results in the literature.

Photoionization of multiply charged ions of the Ba isonuclear sequence up to Ba6+ has been studied in a beam-beam experiment. A very strong increase in the resonance structures was observed when moving from Ba2+ to Ba6+. Absolute values of the photoionization cross sections were measured for Ba2+ and Ba3+ ions. The interpretation of the results is provided using theoretical multiconfiguration Dirac-Fock and relativistic random phase approximation calculations, showing that the collapse of the nf orbitals occurs for Ba4+.

The potential antitumoral effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) led us to evaluate GM-CSF alone or with dacarbazine (DTIC) in metastatic melanoma in first line randomized phase II. Treatment was arm A: GM-CSF: 5 microg kg(-1), bid, 14 consecutive days every 21 days and arm B: GM-CSF: 5 microg kg(-1), bid, day 2 to day 19 every 21 days and DTIC: 800 mg m(-2), day 1 of each cycle. 32 patients (pts) were included, 15 pts in arm A and 17 in arm B. All pts had visceral metastatic sites. 9 had only one metastatic site. The median number of cycles given was 2 in arm A and 3 in arm B. 100% and 89.4% of the planned dose of GM-CSF was given in arm A and arm B respectively. No objective response was obtained. 19 pts experienced at least WHO grade 3 toxicity. All pts had fever, 29 had a decrease in performance status and 23 had pain. Grade 3 toxicity were fever (38.7%), decrease in performance status (32.3%), pain (19.4%) and dyspnoea (12.5%). In this study, GM-CSF alone or in association with DTIC did not induce any antitumoral activity with subsequent toxicity.

The monoclonality of the T cell receptor gamma-chain gene was analyzed by polymerase chain reaction in skin and blood specimens of 85 patients with cutaneous T cell lymphomas including 67 mycosis fungoides, seven Sézary syndromes, and 11 CD30- nonepidermotropic cutaneous T cell lymphomas. A cutaneous T cell clone was detected in 69% of mycosis fungoides and 100% of Sézary syndromes. This frequency varied according to the clinical stage: 57% in early stages (Ia-IIa) to 96% in advanced stages (IIb-IV, Sézary syndrome). A peripheral blood T cell clone was detected in 42% of early stages and in 74% of late stages but was identical to the cutaneous one in 15% and in 63%, respectively. A significant association between initial clinical stage and T cell monoclonality was observed. In nonepidermotropic cutaneous T cell lymphomas, T cell monoclonality was detected in 55% of skin and 36% of blood samples. Univariate and multivariate analyses showed that, besides the initial clinical stage, an identical cutaneous and blood T cell clone was an independent prognostic factor for disease progression of mycosis fungoides/Sézary syndrome (hazard ratio 3.4, 95% confidence interval 1.4-9.9). Parallel polymerase chain reaction study of skin and blood specimens may therefore provide an initial prognostic marker that could help to monitor therapeutic strategies. A fully prospective study, with simultaneous therapeutic trials, needs to be done to confirm our findings and to include treatment variables in the statistical analysis.

Using the trial demonstrating that interferonalpha-2a (IFNalpha-2a) is efficacious as adjuvant therapy in stage II melanoma, we evaluate its outcomes and economic consequences. Using rates observed in the 5-year trial and published figures, survival and Q-TWIST (Time Without Symptoms and Toxicity) were extrapolated to a 10-year and lifetime horizon. Cost analysis was performed using the trial's data, published literature and experts' opinions from the perspective of the French Sickness Funds. Patients in the IFNalpha-2a-group have an additional 0.26 years in life-expectancy over a 5-year time period (P=0.046), 0.67 years over a 10-year period and 2.59 years over a lifetime. Cost per life-year-gained was estimated at approximately 14400 after 5 years, 6635 after 10 years and 1716 over a lifetime. Assuming that there is an improvement in disease-free survival only, cost is 26147 per Q-TWIST. Cost-effectiveness of IFNalpha-2a in stage II melanoma compares favourably with estimates for widely used therapies in the oncological field.

Background: PUVA treatment for patients with severe psoriasis has been demonstrated to be highly effective. However, an increased risk of nonmelanoma and melanoma skin cancers has been reported. It is generally accepted that the risk of squamous-cell carcinoma (SCC) is significantly increased in patients with long-term PUVA therapy. The role of methotrexate (MTX) and infection with oncogenic human papillomaviruses which may act as cocarcinogens is poorly documented., Case Reports: Two cases of multiple SCCs associated with numerous PUVA keratoses and PUVA freckles after long-term PUVA therapy and subsequent treatment with MTX are presented. In 1 case, the tumor progressed to metastatic SCC. Tumors and scrapings of psoriatic skin lesions were analyzed for the presence of oncogenic human papillomavirus (HPV) genotypes. The genotype of HPV-5, -14 and -20 was detected in scrapings and skin tumors using PCR amplification., Conclusion: These observations support the concept that long-term PUVA treatment is carcinogenic and rise questions concerning an additional influence of MTX in the development and progression of skin cancer. The risk of metastatic SCC seems to be underestimated in high-dose PUVA-treated patients due to longer latency for developing metastases and the small number of studies with long-term follow-up. Treatment with MTX should be considered cautiously in patients previously exposed to high doses of PUVA. The presence of oncogenic HPVs in carcinomas and psoriatic skin lesions detected only with the highly sensitive nested PCR method is not necessarily a proof of their implication in skin carcinogenesis., (Copyright 2001 S. Karger AG, Basel.)

AlphaIFN has recently been recognized as an adjuvant therapy to surgery in melanoma patients. A major issue is to select patients who will benefit from this therapy and to avoid toxicity in those who will not respond. The aim of this exploratory analysis was to identify the predictive factors of response to alphaIFN. The French cooperative group has recently shown that adjuvant therapy of melanoma patients with low-dose alphaIFN provides a benefit on disease-free interval (DFI). Using this database, predictors of DFI were investigated using Cox models and treatment-covariate interactions were sought. Gender, age, Breslow thickness, and baseline WBC count, given an alphaIFN-WBC interaction, were independent predictors of DFI. Baseline WBC count was the only variable for which there was an interaction with alphaIFN, whatever the Breslow: patients with low WBC count (<6.8 x 10(9)/liter = median) did not benefit from alphaIFN (HR=1.27 (95%CI: 0.84-1.91); P = 0.26) whereas the DFI of patients with high WBC was prolonged (P = 0.0001) with a hazard ratio of 0.50 (95% confidence interval, 0.35-0.71). The estimated values of WBC count for which IFN was significantly superior to no-treatment were those > or = 7.2 x 10(9)/liter. The baseline WBC count was correlated to baseline neutrophils but not to Breslow thickness or to time since last melanoma surgery. AlphaIFN prolonged DFI in patients with a high WBC count but not in those with a low WBC count. The results of this exploratory analysis, if confirmed by other studies, may help to identify patients who are most likely to benefit from alphaIFN.

Presentation of cell-associated antigen to T cells is a critical event in the initiation of an anti-tumor immune response but it appears to often be deficient or limiting. Here we report an experimental system for stimulation of human T lymphocytes using autologous antigen presenting cells (APCs) and autologous tumor cells. Two types of APCs were prepared from human bone marrow: MC and DC. MC were produced by using GM-CSF and SCF. DC were obtained with the same cytokines plus IL-4. DC and MC were generated in parallel from the same patients and their phenotypes and capacities to prime T lymphocytes were analyzed and compared. MC were CD14+, CD1a-, CD33+ and HLA-DR+. Two populations of DC were defined: immature DC were uniformly CD1a-; mature DC expressed CD1a, CD80, CD86, HLA-DR, CD54 and CD58 but lacked surface CD14. Stimulation of autologous T lymphocytes was studied by measuring their proliferation and cytotoxic function. In more than 80% of our experiments the proliferation of autologous T lymphocytes cocultured with APC pulsed or not with tumor cell lysates was higher than that of T cells cultured alone. DC were more effective than MC in stimulating proliferation of lymphocytes. The capacity of a patient's autologous bone marrow-derived APC to stimulate T cells when exposed to autologous tumor cell lysates suggest that such antigen-exposed APC may be useful in specific anti-tumor immunotherapy protocols., (Copyright 2000 Wiley-Liss, Inc.)

A prospective survey was conducted to assess physician responsibility in melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a standardized questionnaire. Main outcome measures were medical components of the delay before tumor resection and tumor thickness. Of 590 melanomas, 29.1% were coincidentally detected by physicians and their tumor depth was lower than in melanomas detected by patients (p < 0.001). Physician sensitivity for melanoma diagnosis was evaluated at 86%. Median time intervals to propose resection and to perform removal of melanoma were short: 0 (mean 103) and 7 (mean 68) days, respectively. Melanomas were managed in an inappropriate way in 14.2% of cases. Location on acral areas and absence of pigmentation were associated with longer medical delays and more frequent inappropriate medical attitudes. Melanomas located on hardly visible areas were less frequently detected by physicians than those on visible areas. Medical delays were shorter, doctor's attitude was more frequently appropriate, and melanoma thickness was lower (p < 0.001) when the patient visited a dermatologist (54.7%) than when he or she visited a general practitioner (33.4%). Our study shows that doctor responsibility accounts for only a small part of the total delay before melanoma removal. However, systematic total examination and better training of doctors, especially about unusual forms of melanoma, could still improve melanoma detection., (Copyright 2000 Wiley-Liss, Inc.)

A prospective survey was conducted to assess the role of patients in the melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a comprehensive questionnaire including a psychological instrument. Main outcome measures were the delay before medical intervention and the tumor thickness. Of 590 melanomas, 70.8% were detected by patients and this proportion was higher in females. Relatives were involved in the detection of half of the cases. Median delays before the patient realized he had a suspicious lesion, before this lesion was seen by a doctor, and before the melanoma was removed were 4 months, 2 months, and 1 week, respectively. Delays up to several years were observed in some cases. The rate of self-detection tended to be lower, the delays before seeking medical advice to be longer, and the tumor thickness to be higher in old people, in males, in lower-educated individuals, in those living out of towns, and in people with a low awareness about melanocytic tumors than in other cases. Conversely, individuals with a high number of atypical nevi, those who were aware to be at risk, and those who regularly visited a dermatologist tended to detect their melanoma more rapidly. No specific psychological traits were associated with a late reaction, although negligence and anxiety tended to prolong the delays. Knowledge about melanoma was poor in many patients, especially in males, and wrong beliefs were widespread. This study provides the targets of future education programs., (Copyright 2000 Wiley-Liss, Inc.)